The Neurochemistry of Brain Rhythms: Alterations Affecting Attention and Motor Capacity in Parkinson’s Disease
Our latest study, Associations Between Neuromelanin Depletion and Cortical Rhythmic Activity in Parkinson’s Disease, is now published open access in the journal Brain. This work uncovers how changes in specific brain rhythms—critical for cognition and movement—are connected to neurochemical alterations in Parkinson’s disease (PD). These fundamental findings provide new insights into the mechanisms underlying the disease and could inspire translational research into improved diagnostic and therapeutic strategies.
What Did We Discover?
Parkinson’s disease is more than a movement disorder—it also significantly affects cognition and attention. Our study highlights two key findings:
Heightened Alpha Rhythms and Attention Impairments:
Patients with reduced levels of neuromelanin in the locus coeruleus—a brainstem region essential for producing norepinephrine (a neurotransmitter that supports attention and arousal)—showed heightened activity in the frontal and motor areas of the brain.
This heightened activity was observed in the alpha rhythm (8–12 Hz), which is typically the dominant brain rhythm in healthy individuals. The changes were more pronounced in patients with worse attention, suggesting that locus coeruleus degeneration and disrupted norepinephrine signaling contribute to cognitive challenges in PD. This highlights a potential noradrenergic pathway (linked to norepinephrine function) involved in attention impairments.
Weakened Beta Rhythms and Motor Impairments:
Lower neuromelanin in the substantia nigra, another brainstem region rich in dopamine (a neurotransmitter crucial for movement control), was associated with reduced beta rhythms (15–29 Hz) in the motor cortex.
Beta rhythms are dominant in the healthy motor cortex and help regulate voluntary movements. The reduction in beta activity was closely tied to movement impairments, even when patients were taking dopamine-based treatments, emphasizing the critical role of the substantia nigra in motor symptoms of PD.
Why Does This Matter?
These findings deepen our understanding of how Parkinson’s disease affects brain activity and reveal distinct pathways linking neurochemical changes to specific symptoms:
Neuromelanin and Brain Rhythms: Neuromelanin is a pigment that accumulates in dopamine- and norepinephrine-producing neurons. Its loss in the locus coeruleus disrupts norepinephrine signaling, which may lead to heightened alpha activity and cognitive impairments. In the substantia nigra, neuromelanin loss disrupts dopamine signaling, possibly weakening beta rhythms and causing motor impairments.
New Cognitive Insights: This is the first study to link alpha rhythms to locus coeruleus degeneration in PD, offering new insights into the origins of cognitive symptoms like attention deficits.
Motor Pathway Confirmation: While beta rhythm changes in PD have been documented, our study solidifies their connection to substantia nigra degeneration and movement difficulties, even in patients on dopamine therapy.
A Step Toward Tailored Interventions
Our study opens the door to innovative diagnostic and therapeutic approaches:
Dynamic Monitoring of Disease Progression: Using time-resolved neuroimaging techniques like magnetoencephalography (MEG), clinicians could track changes in alpha and beta rhythms to monitor disease progression or treatment efficacy. This approach is more sensitive to dynamic brain changes compared to static brain imaging methods like MRI.
New Therapies for Cognitive Symptoms: Combining norepinephrine-targeted pharmacotherapies (e.g., atomoxetine, a norepinephrine reuptake inhibitor) with brain stimulation techniques such as transcranial alternating current stimulation (tACS) could improve attention and cognitive symptoms in PD. Future studies can explore the potential synergy of these treatments.
Read the full story here.
We are deeply grateful to our study participants and the organizations that supported this work, including the Quebec Parkinson Network (QPN) and Prevent-AD research initiatives.